Synthetic Transformations of Higher Terpenoids. 45#. Regioselective Synthesis of 5-Labdanoid-Substituted Pyrazoles and Assessment of Their Analgesic Activity

A method for targeted structural modification of the methyl ester of phlomisoic acid was developed by introduction of an additional C-16 ketopyrazole moiety via cyclocondensation of diterpenoid alkyne-1,2- diones with arylhydrazines. The conditions for regioselective formation of labdanoid 1,3-diarylpyrazol-5- ylmethanones were found. The possibility of a sequential four-component reaction in a single pot was demonstrated. Significant analgesic activity of labdanoid-substituted diarylpyrazoles in thermal and chemical irritation models was established.